GCS induces multidrug resistance by regulating apoptosis-related genes in K562/AO2 cell line

Cancer Chemotherapy and Pharmacology
Yan LiuPing Xie

Abstract

We have previously shown that the expression of glucosylceramide synthase (GCS) gene in drug-resistant K562/AO2 human leukemia cell was higher than that in drug-sensitive K562 cell, and the sensitivity to adriamycin of K562/AO2 cell was enhanced by inhibiting GCS. It is concluded that the overexpression of GCS gene is one of the reasons which lead to multidrug resistance (MDR) of leukemia cell. Meanwhile, we also found that higher expression of Bcl-2 gene and protein were exhibited in K562/AO2 cell compared with K562 cell. Basing on this, we hypothesized that the high expression of GCS gene which results in MDR of leukemia cell is correlated with Bcl-2 signal transduction. In order to validate the hypothesis, the inhibition of GCS gene in K562/AO2 cell was observed by using chemical suppressor PPMP and siRNA targeted at GCS, and applying RT-PCR and flow cytometry, the expression levels of apoptosis-related gene Bcl-2 and Bax were analyzed before and after inhibiting GCS gene in K562/AO2 cell. The results demonstrated that the gene and protein of Bcl-2 in K562/AO2 cell were both down-regulated significantly after GCS gene being inhibited; however, the Bax mRNA expression had no apparent change in different groups. This suggested...Continue Reading

References

Dec 1, 1986·Proceedings of the National Academy of Sciences of the United States of America·K H CowanC E Myers
May 28, 1996·Proceedings of the National Academy of Sciences of the United States of America·J ZhangY A Hannun
Aug 9, 1996·The Journal of Biological Chemistry·Y LavieM C Cabot
Jan 23, 1997·Nature·A J MinnC B Thompson
Apr 29, 1998·Annual Review of Physiology·R N Kolesnick, M Krönke
Dec 29, 1998·The Journal of Biological Chemistry·D L MarksR E Pagano
Feb 26, 1999·Biochemical Pharmacology·N S Radin
May 12, 2000·Journal of Tongji Medical University = Tong Ji Yi Ke Da Xue Xue Bao·B YueZ Xiang
Jun 22, 2000·International Journal of Cancer. Journal International Du Cancer·J W KokM Müller
Mar 1, 2006·Molecular Cancer Therapeutics·David E ModrakDavid M Goldenberg

❮ Previous
Next ❯

Citations

Jul 14, 2011·Leukemia & Lymphoma·Rebecca J WattersThomas P Loughran
Mar 20, 2012·Journal of Experimental & Clinical Cancer Research : CR·Min SongGuanrui Yang
Oct 18, 2012·Cancer Chemotherapy and Pharmacology·Melis Kartal YandımYusuf Baran
Sep 5, 2020·Molecular Biology Reports·Sweta GhoshSubrata Majumdar
Jun 13, 2015·Molecular Cancer Therapeutics·Jong-Lyel RohJi Won Kim

❮ Previous
Next ❯

Related Concepts

Related Feeds

BCL-2 Family Proteins

BLC-2 family proteins are a group that share the same homologous BH domain. They play many different roles including pro-survival signals, mitochondria-mediated apoptosis and removal or damaged cells. They are often regulated by phosphorylation, affecting their catalytic activity. Here is the latest research on BCL-2 family proteins.

Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis

Antimicrobial Resistance (ASM)

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.

Antimicrobial Resistance

Antimicrobial resistance poses a significant threat to the continued successful use of antimicrobial agents for the treatment of bacterial infections.